News and updates from palliativedrugs.com
- 1Department of Palliative Medicine, University of Nottingham, Nottingham, UK
- 2palliativedrugs.com, Hayward House Study Centre, Nottingham, UK
- Correspondence to Andrew Wilcock, Department of Palliative Medicine, University of Nottingham, Hayward House, Nottingham University Hospitals NHS Trust, Nottingham NG5 1PB, UK;
www.palliativedrugs.com has provided essential independent information about drugs used in palliative and hospice care for over a decade. It contains the on-line Palliative Care Formulary (PCF), and provides free access to a Bulletin Board to stimulate questions and share experiences, a Document Library containing 450 items of useful information and a Syringe Driver Survey Database containing details of over 2350 different drug combinations. Territory-specific book versions (the UK Palliative Care Formulary 4th edition, Hospice and Palliative Care Formulary USA 2nd edition and Palliative Care Formulary Canadian edition) and an e-book PDF version of the PCF can also be purchased via the website. This feature provides a selection of items which have featured in the News and Latest Additions sections in recent months; for additional information please register for free on the website.
EMA review of cardiovascular safety of NSAIDs
The European Medicines Agency (EMA) has finalised a review of recently published information on the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs). The review confirms the findings from previous reviews which concluded that the overall benefit-risk balance of NSAIDs remained positive, but that a small increased cardiovascular risk could not be excluded.
Most of the data related to diclofenac, ibuprofen and naproxen. The latest evidence continues to find a small increase in the risk of cardiovascular undesirable effects for diclofenac compared with other non-selective NSAIDs, similar to the risks of COX-2 inhibitors, particularly with long-term use of high doses and in patients already at high risk. Warnings are already included in the Summary of Product Characteristics (SPC). However, the EMA will now assess all available data on diclofenac (both published and unpublished) to consider the need for updated treatment advice. In relation to naproxen and ibuprofen, the current treatment advice adequately reflects the knowledge regarding their safety and efficacy.
Fatal cases of severe symptomatic hypocalcaemia with denosumab
The UK Medicines and Healthcare products Regulatory Agency (MHRA) have highlighted cases of severe symptomatic hypocalcaemia that have occurred in patients receiving denosumab 120 mg (Xgeva; authorised for use in prevention of skeletal related events in adults with bone metastases from solid tumours) or 60 mg (Prolia; authorised for use in osteoporosis).
Hypocalcaemia is a known risk with denosumab use, especially in patients with severe renal impairment (creatinine clearance <30 ml/min) or receiving dialysis. Severe symptomatic hypocalcaemia, including three fatal cases, has been reported in patients receiving denosumab 120 mg. Although hypocalcaemia with denosumab most commonly occurs within the first 6 months of dosing, it can occur at any time during treatment.
Pre-existing hypocalcaemia must be corrected prior to initiating denosumab, and supplementation of calcium and vitamin D is required in all patients receiving the 120 mg dose unless hypercalcaemia is present. Periodic monitoring of calcium levels (at the discretion of the prescriber) is recommended after use of denosumab in patients predisposed to hypocalcaemia, including those with severe renal impairment.
FDA warn of skin injury with over-the-counter rubefacients
Rare cases of serious burns on the skin have been reported to the US Food and Drug Administration (FDA) where over-the-counter topical muscle and joint pain relievers were applied. The products contained the active ingredients menthol, methyl salicylate, or capsaicin.
MHRA alert: chlorhexidine risk of anaphylaxis
The UK MHRA has issued an alert for products or medical devices containing chlorhexidine following reports of anaphylaxis. Examples of products which contain chlorhexidine are: antiseptic creams, wipes, cleansers and skin preparations; antiseptic mouthwashes, toothpastes and dental implants; eye drops and contact lens solutions; antiseptic lozenges and throat sprays; urinary catheters; central venous catheters; and antimicrobial dressings.
WHO scoping document available for persistent pain in adults
A scoping document for guidelines for the drug treatment of persistent pain in adults has been published by the WHO. Subject to the availability of funding, it is anticipated that these guidelines will be ready by early 2015.
Paediatric morphine doses
WHO have highlighted that the new dosage guidelines for morphine in their 2012 Guidelines on the drug treatment of persistent pain in children with medical illnesses, have a more cautious approach. They replace the dosage recommendations in the WHO Model Formulary for children (2010).
EMA to review safety of codeine for post-operative pain relief in children
The EMA has started its first safety review of a medicine under the new EU rules on pharmacovigilance. It will consider the safety of codeine-containing medicines for post-operative pain relief in children. This has been initiated at the request of the UK MHRA following concerns over an increased risk of morphine toxicity when codeine is given in this setting (codeine is metabolised to morphine by CYP2D6). In particular, a very small number of cases of rare but fatal or life-threatening respiratory depression have been reported in children who are CYP2D6 ultra-rapid metabolisers and were given codeine after surgical removal of the tonsils or adenoids in the treatment of obstructive sleep apnoea.
NICE evidence summary of tranexamic acid off-label use
The UK National Institute for Health and Clinical Excellence (NICE) has published its first evidence summary for the off-label use of products. It is for the use of tranexamic acid for significant haemorrhage following trauma.
Liverpool care pathway independent review and consensus statement
Following a round table discussion, Norman Lamb (UK Minister for Care and Support) is to appoint an independent chair to understand what lies behind the reports of poor quality care associated with the implementation of the Liverpool Care Pathway (LCP) in the UK media and oversee and validate the review work initiated by the National End of Life Care Programme, the Association for Palliative Medicine and Dying Matters. The results of the independent review will be reported next year.
Over 20 organisations have signed a consensus statement in support of the LCP for the dying patient, including professional bodies, third sector organisations, disease specific charities and organisations representing care homes, hospices, social services and palliative care specialists.
Ketamine injection supply problems
Pfizer UK has confirmed that ketamine (Ketalar) 100 mg/ml injection will not be available until November 2014, due to the transfer of the manufacturing site which was beyond their control. Orders for ketamine 10 mg/ml and 50 mg/ml injection are being re-directed to a Pfizer central ordering point (0845 608866), to allow close monitoring of the stock situation.
Oxycodone modified-release generic launched in UK
Qdem Pharmaceuticals (Cambridge, UK) have launched generic oxycodone modified-release 5 mg, 10 mg, 20 mg, 40 mg and 80 mg tablets (Longtec prolonged release). Supplies will come from Bard Pharmaceuticals, the production and supply chain business of Napp Pharmaceuticals. Note: The remains of the m/r tablet may appear in the patient's faeces (often known as ‘ghost tablets’), as can also occur with Oxycontin (Napp, Cambridge, UK). These are inert residues, and do not affect the efficacy of the products.
Epistatus product description change
The product description of the unauthorised (unlicensed) midazolam product Epistatus (Special Products Limited; Weybridge, Surrey, UK) is now described as an oromucosal solution rather than a buccal solution that is, Midazolam (Epistatus) 10 mg in 1 ml Oromucosal Solution×5 ml.
Paracetamol overdose: new guidance on treatment
New simplified guidance on the treatment of acute paracetamol overdose with acetylcysteine is now in place following an evidence-based review by the Commission on Human Medicines in the UK. Full details can be found in the MHRA September 2012 Drug Safety Update.
Hydromorphone ER 32 mg launched in US
A once daily modified-release hydromorphone 32 mg tablet (Exalgo; Mallinckrodt, Hazelwood, Missouri, USA) has been added to the existing product range of 8 mg, 12 mg and 16 mg modified-release tablets for opioid-tolerant adult patients with moderate to severe chronic pain in the US.
Change of supplier for Epanutin (phenytoin) capsules
Flynn Pharma has taken over the manufacture and distribution of Epanutin (phenytoin) capsules in the UK, with the product now marketed as Phenytoin sodium Flynn hard capsules (a generic). Phenytoin sodium Flynn hard capsules are bioequivalent to Epanutin and the capsules have markings and colourings exactly like Epanutin capsules, including still having the marking ‘Epanutin’. Prescribers are advised to specify the Flynn Pharma product when ordering as pharmacies cannot give the Flynn Pharma product against a prescription for Epanutin and will need to get the prescription amended. Concern has been raised in the media regarding the significant cost increase from £0.66 for a pack of 28×25 mg capsules to £15.74.
Metolazone tablets (Sanofi Aventis) have been discontinued by the manufacturer in the UK. There is currently no other supplier of metolazone tablets in the UK. The British Society for Heart Failure has advised switching patients from metolazone to bendroflumethiazide when a patient's supplies run out, at a dose of 2.5 mg, increasing to 5 mg, if indicated. It is currently unknown if generic manufacturers will subsequently start to supply metolazone.
Suboxone sublingual tablets replaced by sublingual film in US
Sublingual combination tablets containing buprenorphine and naloxone (Suboxone; Reckitt Benckiser, Warren, New Jersey, USA), are being replaced by a sublingual film in the US. The tablet formulation, authorised for maintenance treatment in opioid dependence, is now off-patent and available as a generic product. The manufacturer states that the sublingual film has a faster dissolving rate, a more favourable taste and improved child-safety packaging.
Pecfent in use expiry extended to 60 days
The UK SPC for Pecfent (fentanyl citrate) nasal spray 100 μg/spray and 400 μg/spray has been updated. The in-use expiry of the product has been extended from 14 days to 60 days. The SPC now reads ‘If the product has not been used for 5 days, re-prime by spraying once. Discard bottle 60 days after first opening’.
PDF version of PCF4+ now available!
An e-book PDF version containing the latest content of the on-line PCF as of September 2012 (designated PCF4+) is now available to purchase and download from the website. PCF4+ contains 17 updated monographs and 1 appendix, which supersede the printed PCF4 version. We anticipate publishing a PDF version annually, with the fifth edition of the book (PCF5) in 2014.
PCF monographs updated
The PCF is being continually updated on-line. The following monographs have been updated during November 2012 and the website versions supersede the printed PCF 4th edition book versions: Chapter 7: Demeclocycline hydrochloride and Systemic corticosteroids; Chapter 9: Ascorbic acid and Zinc. A full list of all the monographs updated since the publication of PCF4 can be found on the www.palliativedrugs.com website.
The results of the survey ‘Lidocaine 5% medicated plasters–What is your experience?’ are available to view on the www.palliativedrugs.com website.
Competing interests None.
Provenance and peer review Not commissioned; internally peer reviewed.
- Received 12 December 2012.
- Revision received 12 December 2012.
- Accepted 1 January 2013.
- Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions